Maternal anemia, which affects up to 5% of all pregnancies, places infants at increased risk for stillbirth, hypoxia at birth, or growth retardation in utero. The reasons for these poor outcomes are currently unknown, although insufficient availability of oxygen to the fetus, resulting from the mother's anemic state, may be an important factor. In this research proposal, the hypotheses to be tested are: (1) maternal anemia causea a reduction in fetal oxygen delivery; (2) these reductions in fetal O2 delivery lead to circulatory compensations that enable the fetus to maintain normal oxygen consumption and growth; (3) when such compensations are no longer sufficient for the fetus to maintain normal oxygen consumption, fetal growth is reduced and the pattern of fetal growth is altered; and (4) the altered pattern of fetal growth results from chronic reductions in fetal O2 delivery, which affect O2 delivery and protein synthesis in certain fetal tissues more than in other tissues. Maternal or fetal compensations to anemia include alterations in: uterine blood flow, uterine oxygen extraction, placental gas exchange, fetal hemoglobin concentration, umbilical blood flow, and fetal oxygen extraction. The mother or fetus could use any one or a combination of these responses to maintain an adequate oxygen supply to fetal tissues during maternal anemia. To test our hypotheses, we will measures the effects of chronic reductions in maternal hematocrit on uterine blood flow, O2 delivery, O2 extraction, and O2 consumption as well as on umbilical blood flow and fetal O2 delivery, O2 extraction, and O2 consumption. Blood flows will be measured with the radionuclide-labelled microsphere technique, while the variables of oxygenation will be calculated with modifications of the Fick principle. Our proposal will also assess the effects of maternal anemia on fetal substrate use and growth in both individual organs and the fetus as a whole. These variables will be measured in chronically catheterized pregnant sheep in which maternal hematocrit has been maintained at reduced levels throughout the third trimester. The results of our studies will identify the limits within which the fetus can maintain normal metabolism and growth when the mother is subjected to varying degrees of chronic anemia. These studies should enhance our understanding of the pathophysiology of the intrauterine hypoxia and fetal growth retardation that commonly complicate the pregnancies of chronically anemic women.